The organization of AMPA receptor subunits at the postsynaptic membrane: AMPARs IN CA1

AMPA receptors are the principal mediators of excitatory synaptic transmission in the mammalian central nervous system. The subunit composition of these tetrameric receptors helps to define their functional properties, and may also influence the synaptic trafficking implicated in long-term synaptic plasticity. However, the organization of AMPAR subunits within the synapse remains unclear. Here, we use postembedding immunogold electron microscopy to study the synaptic organization of AMPAR subunits in stratum radiatum of CA1 hippocampus in the adult rat. We find that GluA1 concentrates away from the center of the synapse, extending at least 25 nm beyond the synaptic specialization; in contrast, GluA3 is uniformly distributed along the synapse, and seldom extends beyond its lateral border. The fraction of extrasynaptic GluA1 is markedly higher in small than in large synapses; no such effect is seen for GluA3. These observations imply that different kinds of AMPARs are differently trafficked to and/or anchored at the synapse

The temporal evolution of neutron-capture elements in the Galactic discs

Important insights into the formation and evolution of the Galactic disc(s) are contained in the chemical compositions of stars. We analysed high-resolution and high signal to noise HARPS spectra of 79 solar twin stars in order to obtain precise determinations of their atmospheric parameters, ages ($\sigma$$\sim$0.4 Gyr) and chemical abundances ($\sigma$$<$0.01~dex) of 12 neutron-capture elements (Sr, Y, Zr, Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, and Dy). This valuable dataset allows us to study the [X/Fe]-age relations over a time interval of $\sim$10 Gyr and among stars belonging to the thin and thick discs. These relations show that i) the $s$-process has been the main channel of nucleosynthesis of $n$-capture elements during the evolution of the thin disc; ii) the thick disc is rich in $r$-process elements which suggests that its formation has been rapid and intensive. %; iii) a chemical continuity between the thin and thick discs is evident in the abundances of Ba. In addition, the heavy (Ba, La, Ce) and light (Sr, Y, Zr) $s$-process elements revealed details on the dependence between the yields of AGB stars and the stellar mass or metallicity. Finally, we confirmed that both [Y/Mg] and [Y/Al] ratios can be employed as stellar clocks, allowing ages of solar twin stars to be estimated with an average precision of $\sim$0.5~Gyr

Energy-lowering and constant-energy spin flips : emergence of the percolating cluster in the kinetic Ising model

After a sudden quench from the disordered high-temperature T0 → ∞ phase to a final temperature well below the critical point TF Tc, the nonconserved order parameter dynamics of the two-dimensional ferromagnetic Ising model on a square lattice initially approaches the critical percolation state before entering the coarsening regime. This approach involves two timescales associated with the first appearance (at time tp1 > 0) and stabilization (at time tp > tp1 ) of a giant percolation cluster, as previously reported. However, the microscopic mechanisms that control such timescales are not yet fully understood. In this paper, to study their role on each time regime after the quench (TF = 0), we distinguish between spin flips that decrease the total energy of the system from those that keep it constant, the latter being parametrized by the probability p. We show that observables such as the cluster size heterogeneity H(t, p) and the typical domain size (t, p) have no dependence on p in the first time regime up to tp1 . Furthermore, when energy-decreasing flips are forbidden while allowing constant-energy flips, the kinetics is essentially frozen after the quench and there is no percolation event whatsoever. Taken together, these results indicate that the emergence of the first percolating cluster at tp1 is completely driven by energy decreasing flips. However, the time for stabilizing a percolating cluster is controlled by the acceptance probability of constant-energy flips: tp(p) ∼ p−1 for p 1 (at p = 0, the dynamics gets stuck in a metastable state). These flips are also the relevant ones in the later coarsening regime where dynamical scaling takes place. Because the phenomenology on the approach to the percolation point seems to be shared by many 2D systems with a nonconserved order parameter dynamics (and certain cases of conserved ones as well), our results may suggest a simple and eff Because the phenomenology on the approach to the percolation point seems to be shared by many 2D systems with a nonconserved order parameter dynamics (and certain cases of conserved ones as well), our results may suggest a simple and effective way to set, through the dynamics itself, tp1 and tp in such systems

The organization of amyloid-β protein precursor intracellular domain-associated protein-1 in the rat forebrain

Sustained activity-dependent synaptic modifications require protein synthesis. Although proteins can be synthesized locally in dendrites, long-term changes also require nuclear signaling. Amyloid-β protein precursor intracellular domain-associated protein-1 (AIDA-1), an abundant component of the biochemical postsynaptic density fraction, contains a nuclear localization sequence, making it a plausible candidate for synapse-to-nucleus signaling. We used immunohistochemistry to study the regional, cellular, and subcellular distribution of AIDA-1. Immunostaining was prominent in the hippocampus, cerebral cortex, and neostriatum. Along with diffuse staining of neuropil, fluorescence microscopy revealed immunostaining of excitatory synapses throughout the forebrain, and immunoreactive puncta within and directly outside the nucleus. Presynaptic staining was conspicuous in hippocampal mossy fibers. Electron microscopic analysis of material processed for postembedding immunogold revealed AIDA-1 label within postsynaptic densities in both hippocampus and cortex. Together with previous work, these data suggest that AIDA-1 serves as a direct signaling link between synapses and the nucleus in adult rat brain

Multi-Instrument Assessment of Phytoplankton Abundance and Cell Sizes in Mono-Specific Laboratory Cultures and Whole Plankton Community Composition in the North Atlantic

publishedVersio

The time delay of the quadruple quasar RX J0911.4+0551

We present optical lightcurves of the gravitationally lensed components A (=A1+A2+A3) and B of the quadruple quasar RX J0911.4+0551 (z = 2.80). The observations were primarily obtained at the Nordic Optical Telescope between 1997 March and 2001 April and consist of 74 I-band data points for each component. The data allow the measurement of a time delay of 146 +- 8 days (2 sigma) between A and B, with B as the leading component. This value is significantly shorter than that predicted from simple models and indicates a very large external shear. Mass models including the main lens galaxy and the surrounding massive cluster of galaxies at z = 0.77, responsible for the external shear, yield H_0 = 71 +- 4 (random, 2 sigma) +- 8 (systematic) km/s/Mpc. The systematic model uncertainty is governed by the surface-mass density (convergence) at the location of the multiple images.Comment: 12 pages, 3 figures, ApJL, in press (June 20, 2002

Is it possible to separate the graft-versus-leukemia (GVL) effect against B cell acute lymphoblastic leukemia from graft-versus-host disease (GVHD) after hematopoietic cell transplant?

Hematopoietic cell transplant is a curative therapy for many pediatric patients with high risk acute lymphoblastic leukemia. Its therapeutic mechanism is primarily based on the generation of an alloreactive graft-versus-leukemia effect that can eliminate residual leukemia cells thus preventing relapse. However its efficacy is diminished by the concurrent emergence of harmful graft-versus-host disease disease which affects healthly tissue leading to significant morbidity and mortality. The purpose of this review is to describe the interventions that have been trialed in order to augment the beneficial graft-versus leukemia effect post-hematopoietic cell transplant while limiting the harmful consequences of graft-versus-host disease. This includes many emerging and promising strategies such a

Cortisol as an Acute Stress Biomarker in Young Hematopoietic Cell Transplant Patients/Caregivers: Active Music Engagement Protocol

Objective: Primary aims of the proposed protocol are to determine the feasibility/acceptability of the active music engagement intervention protocol during hematopoietic stem cell transplantation (HSCT) and clinical feasibility/acceptability of the biological sample collection schedule. Design: The authors propose a single-case, alternating treatment design to compare levels of child and caregiver cortisol in blood and saliva collected on alternating days, when the dyad receives and does not receive AME sessions. Included are the scientific rationale for this design and detailed intervention and sample collection schedules based on transplant type. Setting/Location: Pediatric inpatient HSCT unit. Subjects: Eligible participants are dyads of children 3-8 years old, hospitalized for HSCT, and their caregiver. Children with malignant and nonmalignant conditions will be eligible, regardless of transplant type. Intervention: AME intervention is delivered by a board-certified music therapist who tailors music-based play experiences to encourage active engagement in, and independent use of, music play to manage the inter-related emotional distress experienced by children and their caregivers during HSCT. Dyads will receive two 45-min AME sessions each week during hospitalization. Outcome Measures: Eight collections of blood (child) and saliva (child/caregiver) will be performed for cortisol measurement. The authors will also collect self-report and caregiver proxy measures for dyad emotional distress, quality of life, and family function. At study conclusion, qualitative caregiver interviews will be conducted. Results: Planned analyses will be descriptive and evaluate the feasibility of participant recruitment, cortisol collection, planned evaluations, and AME delivery. Analysis of qualitative interviews will be used to gain an understanding about the ease/burden of biological sample collection and any perceived benefit of AME. Conclusions: Behavioral intervention studies examining biological mechanisms of action in pediatric transplant populations are rare. Findings will provide important information about the feasibility/acceptability of collecting cortisol samples during a high-intensity treatment and advance understanding about the use of active music interventions to mitigate child/caregiver distress during the transplant period